Abstract HIV-1 integrase (IN) is a key target in the viral life cycle for the development of new therapeutics. Despite the successful development of FDA approved active site inhibitors like raltegravir, elvitegravir, and dolutegravir, resistance to these agents threatens their long-term utility. Allosteric IN inhibitors that bind at the LEDGF/p75 site of IN represent an alternative strategy for the development of compounds that will not share the same resistance profile. These allosteric inhibitors have recently been shown to affect IN activity through promotion of aberrant multimerization, a process that is still not well understood. It is believed that binding to the LEDGF/p75 pocket within the CCD dimer interface of IN induces the recruitment of another IN protein that then is able to bind at this site, resulting in the formation of an inactive higher order oligomer. The current proposal is focused on the development of compounds designed to probe the IN CCD dimer/CTD interface in an effort to more efficiently ?catalyze? this process, leading to the inhibition of IN. A key component of this proposal is also the development of a completely new scaffold capable of binding to the LEDGF/p75 pocket and predicted to show a unique resistance profile compared to previously synthesized allosteric inhibitors.